The effect of progesterone on gonadotropin secretion is stimulatory or inhibitory depending on the dose of progesterone used and the time of administration in the estrus cycle or to the estrogen primed castrated rat. Progesterone does not alter gonadotropin secretion in the castrated rat in the absence of estrogens. An animal preparation has been developed in our laboratory using low dose estradiol treatment which induced progesterone sensitivity but does not bring about endogenous LH surges. A single injection of progesterone results in the stimulation or suppression of gonadotropins depending upon the dose of progesterone. Other models using the adult rat and the use of progesterone, 17 alpha hydroxyprogesterone and their 5 alpha and 20 alpha reduced metabolites will be developed to bring about stimulatory, inhibitory, or divergent patterns of FSH and LH release. The effect of these steroids on the secretion of LHRH by the hypothalamus will be evaluated by measuring media basal hypothalamic LHRH, blood LHRH and serum FSH and LH. Methods for measuring LHRH turnover will be explored and sites of synthesis located by immuocytochemical techniques and quantified by RIA after isolation of specific areas by the punch technique described by Palhowits. The functional correlation between estrogen receptors, progesterone receptors, LHRH binding sites and the pituitary sensitivity in LHRH will be examined during different patterns of FSH and LH release. The effect of progesterone on cytoplasmic and nuclear estrogen receptors, their molecular forms, ability to translocate in the nucleus, nuclear retention, and replenishment will be studied in detail. Similar studies will be done with the progesterone receptor in attempts to determine the effect of estrogen as well as progesterone on progesterone receptor dynamics.